ArticleMolecular and cellular biology2002
TRAP/SMCC/mediator-dependent transcriptional activation from DNA and chromatin templates by orphan nuclear receptor hepatocyte nuclear factor 4.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 96 citations in OpenAlex.
- Nuclear receptor coregulator interactions: beyond the switch.Genes & development · 2026Review
- The Mediator Complex: A Regulatory Hub for Transcriptional Activity of Nuclear Receptors.Cells · 2025Review
- Unique and overlapping roles of NRF2 and NRF1 in transcriptional regulation.Journal of clinical biochemistry and nutrition · 2024Article
- The Mediator complex as a master regulator of transcription by RNA polymerase II.Nature reviews. Molecular cell biology · 2022Review
- Structure of the human Mediator-bound transcription preinitiation complex.Science (New York, N.Y.) · 2021Article
- LncRNA Lnc-APUE is Repressed by HNF4Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Molecular determinants of MED1 interaction with the DNA bound VDR-RXR heterodimer.Nucleic acids research · 2020Article
- ErbB3-binding protein 1 (EBP1) represses HNF4α-mediated transcription and insulin secretion in pancreatic β-cells.The Journal of biological chemistry · 2019Article
- Review
- Gene-Specific H1 Eviction through a Transcriptional Activator→p300→NAP1→H1 Pathway.Molecular cell · 2019Article
- Transcription regulation by the Mediator complex.Nature reviews. Molecular cell biology · 2018Review
- Toward understanding of the mechanisms of Mediator function in vivo: Focus on the preinitiation complex assembly.Transcription · 2017Review
- Diabetes-linked transcription factor HNF4α regulates metabolism of endogenous methylarginines and β-aminoisobutyric acid by controlling expression of alanine-glyoxylate aminotransferase 2.Scientific reports · 2016Article
- FOXA and master transcription factors recruit Mediator and Cohesin to the core transcriptional regulatory circuitry of cancer cells.Scientific reports · 2016Article
- The Mediator complex: a central integrator of transcription.Nature reviews. Molecular cell biology · 2015Review
- Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases.Journal of experimental neuroscience · 2015Review
- Reconstitution of active human core Mediator complex reveals a critical role of the MED14 subunit.Nature structural & molecular biology · 2014Article
- Article
- Aberrant regulation of FBW7 in cancer.Oncotarget · 2014Review
- Mechanisms of Mediator complex action in transcriptional activation.Cellular and molecular life sciences : CMLS · 2013Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The orphan nuclear receptor hepatocyte nuclear factor 4 (HNF-4) regulates the expression of many liver-specific genes both during development and in the adult animal. Towards understanding the molecular mechanisms by which HNF-4 functions, we have established in vitro transcription systems that faithfully recapitulate HNF-4 activity. Here we have focused on the coactivator requirements for HNF-4, especially for the multicomponent TRAP/SMCC/Mediator complex that has emerged as the central regulatory module of the transcription apparatus. Using a system that has been reconstituted from purified transcription factors, as well as one consisting of unfractionated nuclear extract from which TRAP/SMCC/Mediator has been depleted by specific antibodies, we demonstrate a strong dependence of HNF-4 function on this coactivator. Importantly, we further show a TRAP/SMCC/Mediator-dependence for HNF-4 transcriptional activation from chromatin templates. The latter involves cooperation with the histone acetyltransferase-containing coactivator p300, in accord with a synergistic mode of action of the two divergent coactivators. We also show that HNF-4 and TRAP/SMCC/Mediator can interact physically. This interaction likely involves primary HNF-4 activation function 2 (AF-2)-dependent interactions with the TRAP220 subunit of TRAP/SMCC/Mediator and secondary (AF-2-independent) interactions with TRAP170/RGR1. Finally, recruitment experiments using immobilized templates strongly suggest that the functional consequences of the physical interaction probably are manifested at a postrecruitment step in the activation pathway.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.